C. difficile is a leading cause of antibiotic-associated diarrhea and nosocomial infection. Antibiotic treatment is the standard approach in managing C. difficile infection (CDI) and is associated with recurrence rates of up to 65% depending on the number of previous disease. Alanyl-glutamine prevents C. difficile toxin-induced impairment of cell migration and proliferation in intestinal cell lines, secretion and histopathology in animal ieal tissues, and increased apoptosis in vitro and in vivo. Recently, we have shown that in the mouse model of CDI, alanyl-glutamine supplementation significantly reduced diarrhea, weight loss, histopathology, relapse and deaths in vancomycin-treated mice. We hypothesize that supplementation with alanyl-glutamine will improve outcomes of treatment of CDI in humans. To prove this hypothesis, the planned clinical trial will have 2 specific aims. First, we shall test te effect of oral supplementation with alanyl-glutamine on duration of diarrhea, recurrence and deaths in patients treated with standard anti-C.difficile agents. Secondly, we shall test the effec of alanyl-glutamine on intestinal inflammation, barrier function and gut flora in patients undergoing standard treatment for CDI. To adequately prepare for the clinical trial, this proposal will have the following specific aims: (1) Establish and prepare the research team to run the clinical trial; (2) Develop documents needed for the clinical trial; and (3) Develop tools that are required for the evaluation of the clinical trial. The planning grant will allow for a rigorous, sae, effective and productive performance of the clinical trial to prove the benefit of alanyl-glutamine in human disease, potentially introducing a novel approach to treatment of CDI.